Excessive formation of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, has been implicated in the development of insulin resistance in obesity and type-2 diabetes. In skeletal muscle, chronic exposure to TNF-α impairs insulin-stimulated glucose uptake and insulin signaling. The aim of this study is to investigate the effects of enzymatic egg white hydrolysate (EWH) and its responsible peptide, IRW, on TNF-α-induced insulin resistance and the underlying molecular mechanisms using rat skeletal muscle cells (L6 cells).,Insulin resistance was induced by treating L6 cells with 5 ng/ml TNF-α for 24 h. Effects of EWH and IRW on glucose uptake were detected by glucose uptake assay, glucose transporter 4 (GLUT4) translocation by immunofluorescence, and western blot, while insulin-signaling pathway and mitogen-activated protein kinase (MAPK) pathway were investigated using western blot.,Adding both EWH and IRW significantly improved glucose uptake in TNF-α-treated cells, increased activation of insulin receptor substrate (IRS-1) tyrosine residue and protein kinase B (Akt), whereas decreased activation of IRS-1 serine residue. In addition, TNF-α-induced activation of p38-mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNK) 1/2 were decreased by either EWH or IRW treatment.,EWH and IRW improve impaired insulin sensitivity by down-regulating the activation of p38 and JNK1/2 in TNF-α-treated skeletal muscle cells.